The mechanisms of binding and entry of varicella zoster virus (VZV) into cells are unknown. We are investigating the binding of VZV to cell membrane preparations from a variety of cultured cell-lines, to isolated proteins, glycoconjugates, and to synthetic peptides. Inhibition of VZV infectivity in diploid human lung cells in being used assess potential receptor-mimicking molecules for ability to block VZV binding and infection of cells. Monoclonal and polyclonal antibodies to cell membrane proteins are being developed to identify the specific cell surface molecules that serve as receptors for VZV. We have found that heparin inhibited infectivity of VZV in contrast another glycosaminoglycan chondroitin sulfate did not inhibit VZV infectivity. VZV binding to cell membrane preparations was measured. VZV binding was inhibited by added heparin suggesting that an important mechanism of interaction of VZV with cells involves heparin. Several assays were developed to measure binding of VZV and of herpesvirus glycoproteins to immobilized heparin. VZV was found to bind to immobilized heparin. Soluble VZV gB (gpII) has been produced using the vaccininia-T7 expression system to investigate glycoprotein to heparin receptor binding using ELISA based and biosensor technologies. This system will allow identification of glycoprotein structures critical to interaction between VZV and heparin receptors of cells.